Nordihydroguaiaretic acid affects multiple dynein-dynactin functions in interphase and mitotic cells
Nordihydroguaiaretic acid affects multiple dynein-dynactin functions in interphase and mitotic cells
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DOI：
10.1124/mol.106.029611
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Tagaya, Mitsuo
中科院分区：
文献类型：
--
作者：
Arasaki, Kohei;Tani, Katsuko;Tagaya, Mitsuo
去甲二氢愈创木酸（NDGA）是一种脂氧合酶抑制剂，对细胞具有多种作用，包括细胞增殖、凋亡、分化和趋化性。我们和其他人以前已经表明，这种化合物通过一种未知的机制导致高尔基体解体。在这项研究中，我们表明，在平行的高尔基体解体，NDGA诱导微管负端定向运动动力蛋白-动力蛋白复合物的积累在中心体，微管负端谎言。伴随着这种积累，动力蛋白-动力肌动蛋白相互作用蛋白，如ZW 10和EB 1，也重新分布到中心体区域。在微管被诺考达唑解聚的细胞中，NDGA促进了由动力蛋白-动力肌动蛋白及其相互作用蛋白组成的细丝的形成，这表明它以有序而非随机的方式刺激这些蛋白质的缔合。丧失dynactin功能不仅废除NDGA诱导的重新分布在完整的细胞，但也丝形成诺考达唑处理的细胞。后者的发现意味着，动力蛋白-动力蛋白和其相互作用蛋白之间的关联，动力蛋白是一个关键分子。在有丝分裂细胞中，NDGA诱导动力蛋白-动力肌动蛋白及其相互作用蛋白在纺锤体两极的大量积累。这些结果共同表明，NDGA通过影响微管运动动力蛋白-动力蛋白复合物及其辅助蛋白的功能来扰乱膜交通。据我们所知，NDGA是第一例可以调节动力蛋白-动力肌动蛋白相关过程的试剂。
Nordihydroguaiaretic acid (NDGA), a well known lipoxygenase inhibitor, actually has pleiotropic effects on cells, which include cell proliferation, apoptosis, differentiation, and chemotaxis. We and others have shown previously that this compound causes Golgi disassembly by an unknown mechanism. In this study, we show that, in parallel with Golgi disassembly, NDGA induces the accumulation of the microtubule minus-end-directed motor dynein-dynactin complex at the centrosome, where microtubules minus-ends lie. Concomitant with this accumulation, dynein-dynactin-interacting proteins, such as ZW10 and EB1, were also redistributed to the centrosomal region. In cells where microtubules were depolymerized by nocodazole, NDGA promoted the formation of filaments consisting of dynein-dynactin and its interacting proteins, suggesting that it stimulates the association of these proteins in an ordered, not random, manner. Loss of dynactin function abolished not only NDGA-induced redistribution in intact cells but also filament formation in nocodazole-treated cells. The latter finding implies that dynactin is a key molecule for the association between dynein-dynactin and its interacting proteins. In mitotic cells, NDGA induced robust accumulation of dynein-dynactin and its interacting proteins at the spindle poles. These results taken together suggest that NDGA perturbs membrane traffic by affecting the function of the microtubule motor dynein-dynactin complex and its auxiliary proteins. To our knowledge, NDGA is the first case of a reagent that can modulate dynein-dynactin-related processes.